Identification of a characteristic morphology of a coronary stenosis likely to result in myocardial infarction would facilitate the prospective evaluation of infarct prevention strategies and identification of high-risk patients. We postulated that coronary lesions associated with recent myocardial infarction or unstable angina would have an angiographic morphology suggesting disruption of an atherosclerotic plaque and would appear morphologically different from lesions associated with chronic stable angina. To test this hypothesis, quantitative coronary angiography (Brown-Dodge method) was performed in 15 patients 4 to 30 days after myocardial infarction, in 10 patients with the abrupt onset of unstable angina and single-vessel coronary disease, and in 15 patients with chronic stable angina without prior myocardial infarction. Serial arterial diameters (20 to 40) within each lesion were determined and the degree of luminal irregularity was quantitated by calculation of an 'ulceration' index. The majority of all lesions analyzed resulted in severe luminal stenosis (mean 78% area stenosis, all groups). Despite small differences in mean lesion severity among groups, overlap in the degree of luminal compromise prevented precise classification of lesions associated with myocardial infarction or unstable angina based on percent stenosis or minimum luminal cross-sectional area. The mean ulceration index of lesions in patients with unstable angina and in the infarct-related vessel in those with acute myocardial infarction was 0.62 ± 0.05 (± SEM) and 0.61 ± 0.03, respectively. These were significantly different from the mean ulceration indexes of lesions in patients with stable angina (0.96 ± 0.01, p < .05) or from indexes of lesions in the noninfarct-related vessel of patients with acute infarction (0.90 ± 0.02, p < .05). None of 10 lesions associated with unstable angina and 14 of 15 infarct-related lesions had an ulceration index less than 0.78. All lesions associated with stable angina and each lesion in the noninfarct-related vessel in patients with infarction had an ulceration index of greater than 0.83. The ulceration index did not vary significantly with the degree of luminal stenosis or prior treatment with thrombolytic agents. These data provide quantitative evidence that lesions associated with myocardial infarction or the abrupt onset of unstable angina are of a similar characteristic angiographic morphology that is suggestive of plaque disruption and not commonly seen in lesions associated with chronic stable angina. The ulceration index may provide a mechanism for the prospective identification of high-risk coronary lesions.